Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2011 May 10;108(19):7838-43. doi: 10.1073/pnas.1103113108. Epub 2011 Apr 26.
The simple yet powerful technique of induced pluripotency may eventually supply a wide range of differentiated cells for cell therapy and drug development. However, making the appropriate cells via induced pluripotent stem cells (iPSCs) requires reprogramming of somatic cells and subsequent redifferentiation. Given how arduous and lengthy this process can be, we sought to determine whether it might be possible to convert somatic cells into lineage-specific stem/progenitor cells of another germ layer in one step, bypassing the intermediate pluripotent stage. Here we show that transient induction of the four reprogramming factors (Oct4, Sox2, Klf4, and c-Myc) can efficiently transdifferentiate fibroblasts into functional neural stem/progenitor cells (NPCs) with appropriate signaling inputs. Compared with induced neurons (or iN cells, which are directly converted from fibroblasts), transdifferentiated NPCs have the distinct advantage of being expandable in vitro and retaining the ability to give rise to multiple neuronal subtypes and glial cells. Our results provide a unique paradigm for iPSC-factor-based reprogramming by demonstrating that it can be readily modified to serve as a general platform for transdifferentiation.
诱导多能性这一简单而强大的技术最终可能会为细胞治疗和药物开发提供广泛的分化细胞。然而，通过诱导多能干细胞（iPS 细胞）制造合适的细胞需要体细胞的重编程和随后的再分化。鉴于这个过程可能非常艰难和漫长，我们试图确定是否有可能一步将体细胞转化为另一个胚层的谱系特异性干细胞/祖细胞，从而绕过中间多能阶段。在这里，我们展示了瞬时诱导这四种重编程因子（Oct4、Sox2、Klf4 和 c-Myc）可以有效地将成纤维细胞转化为具有适当信号输入的功能性神经干细胞/祖细胞（NPC）。与诱导神经元（或 iN 细胞，直接从成纤维细胞转化而来）相比，转分化的 NPC 具有体外可扩增的明显优势，并保持产生多种神经元亚型和神经胶质细胞的能力。我们的研究结果提供了一个基于 iPSC 因子的重编程的独特范例，证明它可以很容易地被修改，作为一个通用的转分化平台。
